Tuberculosis (TB) is one of the most important infectious diseases in humans and animals worldwide. The World Health Organization currently estimates that roughly one-third of the world's population is infected with tuberculosis (TB), caused by the Mycobacterium tuberculosis (Mtb). In the year 2011 alone, 8.7 million people fell ill with TB and another 1.4 million died. While the risk of developing symptoms from the latent condition is only 10%, this number increases greatly if the individual is also infected with an immune compromising disease such as HIV. TB is a treatable and curable disease, typically combated with a six-month course of antimicrobial drugs, and the use of these treatments has significantly decreased the mortality rate for TB over the last quarter century. Despite this, multi-drug resistant TB strains generate concern among medical experts and demand the need for the development of new antimicrobial strategies. One important component to treatment strategies is the implementation of effective and accurate diagnosis and tracking of infections, including latent infections. Such diagnostic strategies could dramatically enhance the ability to detect infection and potentially prevent transmission, thus reducing the overall incidence of TB.
Early diagnosis is critical to the prevention and control of tuberculosis due to its airborne transmission. Standard diagnostic methods, such as an acid-fast stain on smears from sputum, do not become positive until after transmission can occur, allowing spread of disease. Culture-based techniques are more sensitive, but take weeks to obtain results, due to the extremely slow growth rate of TB bacteria. Thus, clinical diagnosis and disease control would be greatly facilitated by methods that can detect tubercle bacteria in a sensitive, rapid, specific and quantitative manner during disease.
In addition to this, the current vaccine, Mycobacterium bovis Bacillus Calmette Guerin (BCG), displays variable efficacy (0-80%) depending on the population being vaccinated. Currently, researchers typically rely on animal studies to help assess the effectiveness of new therapeutic agents. These studies employ sacrifice at discrete time points, tissue homogenization, and colony growth. These factors combine to greatly limit temporal and spatial resolution of the bacteria in tissue. Thus, the development of an experimental technique that could provide rapid feedback regarding the efficacy of a therapeutic agent in an animal model of a respiratory infection could greatly benefit the development of such vaccines.
Despite the advances in the development of diagnostic techniques for the diagnosis and monitoring of TB infections, a need remains for sensitive, rapid, and specific diagnostic reagents and methods that facilitate the rapid detection of tuberculosis. The present invention seeks to fulfill this need and provides further related advantages.